Device for Monitoring Blood Flow to the Brain

ABSTRACT

A method of estimating blood flow in a brain, comprising: a) causing currents to flow inside the head by producing electric fields inside the head; b) measuring at least changes in the electric fields and the currents; c) estimating changes in the blood volume of the head, using the measurements of the electric fields and the currents, where the current are produced in children or using electrodes at or near holes in the skull. Optionally, the configuration is selected to focus the flow of current to be inside the brain to a significant degree.

RELATED APPLICATION

The present application is a continuation in part of U.S. applicationSer. No. 10/893,570, filed on Jul. 15,2004, which is a continuation inpart of PCT Application No. PCT/IL03/00042, filed on Jan. 15, 2003,which also claims the benefit under §119(e) of U.S. ProvisionalApplication No. 60/348,278, filed on Jan. 15, 2002. The presentapplication is also related to a PCT application entitled “CerebralPerfusion Monitor, filed on even date, having attorney docket number371/04418. The disclosures of these applications are incorporated hereinby reference.

FIELD OF THE INVENTION

The field of the invention is medical instrumentation, for example formeasuring blood flow to the brain.

BACKGROUND OF INVENTION

There is a need to measure cerebral blood flow dining several medicalevents and procedures, because any disturbance to the flow of blood tothe brain may cause an injury to the function of the brain cells, andeven death of brain cells if the disturbance is prolonged. Maintainingblood flow to the brain is especially important because brain cells aremore vulnerable to a lack of oxygen than other cells, and because braincells usually cannot regenerate following an injury. A number of commonsituations may cause a decrease in the general blood flow to the brain,including arrhythmia, myocardial infarction, and traumatic hemorrhagicshock. In such cases, data regarding the quantity of blood flow in thebrain, and the changes in flow rate, may be vastly important inevaluating the risk of injury to the brain tissue and the efficacy oftreatment. The availability of such data may enable the timelyperformance of various medical procedures to increase the cerebral bloodflow, and prevent permanent damage to the brain.

Existing means for measuring cerebral blood flow are complex, expensive,and in some cases invasive, which limits their usefulness. Threenon-portable methods that are presently used only in research are: 1)injecting radioactive xenon into the cervical carotid arteries andobserving the radiation it emits as it spreads throughout the brain; 2)positron emission tomography, also based on the injection of radioactivematerial; and 3) magnetic resonance angiography, performed using aroom-sized, expensive, magnetic resonance imaging system, and requiringseveral minutes to give results. A fourth method, trans-cranial Doppler(TCD) uses ultrasound and is not invasive, and gives immediate results.However, TCD fails in about 15% of patients, due to the difficulty ofpassing sound waves through the cranium, and it requires great skill byprofessionals who have undergone prolonged training and practice inperforming the test and deciphering the results. Another disadvantage ofTCD is that it measures only regional blood flow in the brain, and doesnot measure global blood flow.

Impedance measurements of the thorax are a known technique formonitoring intracellular and extracellular fluid in the lungs, inpatients with congestive heart failure. This technique is effectivebecause the resistive impedance of the thorax at low frequency dependson the volume of blood and other electrolytic fluids, which have arelatively high electrical conductivity, present outside cells. (Thecapacitive impedance of the thorax, on the other hand, depends largelyon the volume of fluid inside cells.) A complicating effect in measuringthe impedance of the thorax is the changing volume of air in the lungsduring the breathing cycle, since air has a very high resistivity, andvarious methods have been developed to compensate for this effect. See,for example, U.S. Pat. Nos. 5,788,643, 5,749,369, and 5,746,214, thedisclosures of which are incorporated herein by reference.

In these impedance measurements, current is often passed through thethorax with one set of electrodes, and a different set of electrodes isused to make voltage measurements. This “four wire” method essentiallyeliminates the voltage drop associated with the current flowing throughany impedance in series with the thorax in the current-carrying circuit,for example due to poor contact (possibly changing unpredictably)between the current-carrying electrodes and the skin, or in the powersupply producing the current. Those voltage drops, which are not ofinterest in measuring the impedance of the thorax, do not occur in theseparate voltage-measuring circuit because it has high impedance andvery little current flowing in it.

Photoplesthysmography is another technique used to monitor blood flowand blood volume, using the reflectivity of red or infrared light fromthe surface of the skin, for example the finger, or the earlobe. See,for example, J. Webster, “Measurement of Flow and Volume of Blood,” inJohn G. Webster (ed.), Medical Instrumentation: Application and Design(Wiley, 1997), the disclosure of which is incorporated herein byreference.

Magnetically inducing electrical fields in the body, including the head,is used in some existing medical procedures, principally for stimulationof the peripheral or central nervous system. See, for example, PCTpublication WO 96/16692, the disclosure of which is incorporated hereinby reference. Peripheral nerve stimulation is also a well known unwantedside effect of the time-varying magnetic fields used in magneticresonance imaging.

SUMMARY OF THE INVENTION

As aspect of some embodiments of the invention relates to usingimpedance measurements of at least part of the head to estimate bloodflow to the brain. For some applications, it is not necessary to measurethe absolute impedance accurately, since the blood flow is estimated,and/or the presence of significant blood flow is ascertained, byobserving changes in the impedance (due to changes in blood volume)during a cardiac cycle. For some applications, even the absolute bloodflow rate need not be measured accurately, but it is enough to detectchanges in the blood flow rate over time. Various methods are used tomake the impedance measurements more sensitive to the impedance of thebrain, and less sensitive to the much greater impedance of the skull, aswell as to reduce motion artifacts.

In some embodiments of the invention, the impedance of the head ismeasured by passing current through the head and measuring theassociated voltage by electrodes. To reduce the errors in measurementthat are associated with the high relative impedance of the skull,current is passed through the head using one or more pairs ofcurrent-carrying electrodes, and a separate pair of voltage-measuringelectrodes, on a separate high impedance circuit, is used to measure thevoltage across the head. Optionally, sensitivity to the skull impedanceis further reduced by inserting the voltage measuring electrodes intothe ears. Alternatively or additionally, the nose or other orifices, orthin bone areas in the skull, are used. Examples of orfices are openingsin the skull, for example the eye sockets, or the foramen magnum. Anexample of a thin bone area is the temple.

Optionally, electrodes of large area are used, or one or more electrodesare spread out over a large area (for example, by using an annularelectrode) even if the total area of the electrodes themselves is not solarge, in order to focus the current to go through the interior of thehead, and not so much through the scalp. Optionally, a large voltagesensing area, for example a plurality of voltage-measuring electrodesspread out over a large area and shorted together, or a singlevoltage-measuring electrode with a long, winding shape or with many armsspread out over a large area, is interspersed among a current-carryingelectrode or electrodes similarly spread out over a large area.Optionally, when the distance between the different electrodes, or thedifferent arms of the electrodes, is comparable to or greater than thethickness of the scalp and skull, or even just the thickness of thescalp, then the voltage measured by the voltage-measuring electrode willtend to be relatively insensitive to the voltage drop across the scalpand skull, and will be relatively more sensitive to the voltage dropacross the brain. For example, the individual electrodes, or the aims ofthe electrodes, are at least 1 mm wide, or at least 2 mm wide, or atleast 5 mm wide, or at least 1 cm wide, and the electrodes are separatedby similar distances. The total spread of the electrodes on each, sideof the head, for example, is at least 1 cm, or at least 2 cm, or atleast 5 cm.

Electrodes with width, or spacing, in the smaller part of the rangementioned above may be adapted for use in newborn babies, includingpremature babies. For example, if an individual electrode, or the armsof an electrode, or the separation between electrodes, is between 1 mmand 2 mm, or a somewhat smaller or larger distance, then the distancewill be comparable to the thickness of the scalp of a newborn baby,which is generally between 1 mm and 2 mm. If an individual electrode, orthe arms of an electrode, or the separation between electrodes, isbetween 2 mm and 5 mm, or a somewhat smaller or larger distance, thenthe distance will be comparable to the total thickness of the scalp plusskull of a newborn baby, which is generally between 2 mm and 5 mm.Monitoring the blood flow in the brain of a newborn baby, particularly apremature baby, is important, since the autoregulation mechanism forcerebral blood flow is not well developed, and sudden changes in bloodflow, if not detected and treated immediately, cars lead to seriousbrain damage or death. Impedance measurement of cerebral blood flow,alone or in combination with photoplethysmography, is inexpensive andsimple enough that it is practical to use for continuous monitoring of anewborn baby or any other patient, in contrast to some other methods ofmeasuring cerebral blood flow which require special expensive equipmentand/or people with specialized training to interpret the results.

In an exemplary embodiment of the invention, monitoring includesrecording those treatments, activities and/or times which, for aparticular baby, cause spikes in blood flow. Optionally, such treatmentsare modified to reduce spikes and/or medication is provided at timesand/or activities which induce spikes. Other spike reduction methods maybe used as well. Exemplary treatments or activities which may causespikes include, blood taking, catheterization, load noises, illuminationchanges, feeding and/or moving.

In an exemplary embodiment of the invention, the premature baby weighsless than 2 Kg, less than 1.5 Kg, less than 1 Kg, less than 750 gram orintermediate or lower values. Newborn babies can be, for example, 3.5 Kgor less, such as 3 Kg or 2.5 Kg or less.

In an exemplary embodiment of the invention, measurements on neonatalpatients are performed on openings in the skull, for example where skullplates have not met.

Optionally, the impedance of the head is measured over time. The changein impedance over a pulse cycle, for example, is a measure of the changein blood volume during a pulse cycle, and hence the blood flow rate.Even if there are inaccuracies in the blood flow rate measured in thisway, the technique is adequate for detecting a substantial drop in bloodflow to the brain that occurs during surgery, or in determining whetherCPR is being performed effectively.

In some embodiments of the invention inductive measurements are used toestimate the impedance of the head, and hence the blood volume and rateof blood flow to the brain. One or more coils with alternating currentflowing in them, adjacent to the head, are used to produce a changingmagnetic field inside the head, and hence to induce an electric field,which drives eddy currents in the brain. The magnitude of these eddycurrents depends on the impedance of the brain, and hence on the bloodvolume of the brain. The eddy currents in the brain are measured by thechanging magnetic field, and hence voltage, which they induce in thedriving coils, or in one or more separate measuring coils, which areplaced around the head, approximately parallel to the driving coils.

Optionally, instead of or in addition to using the driving coils ormeasuring coils to measure the eddy currents in the brain,voltage-measuring electrodes on the skin are used to measure the inducedelectric field. Alternatively or additionally, magnetic field sensors,for example Hall sensors, flux gate magnetometers, or SQUIDs, are usedto measure the magnetic field. Both the induced electric field and themagnetic field depend on the impedance of the brain, because the eddycurrents in the brain affect the magnetic field.

An aspect of some embodiments of the invention concerns the use ofphotoplethysmography to estimate the rate of blood flow to the brain,either alone or in conjunction with impedance measurements. Optionally,photoplethysmography is performed, inside the ear, which makes it moresensitive to the important internal blood flow in the head, as opposedto measurements in the earlobe which depend on peripheral blood flow. Aprobe for photoplethysmography inside the ear is optionally combinedwith a voltage-measuring probe used inside the ear for impedancemeasurements.

There is thus provided, in accordance with an embodiment of theinvention, a method of estimating blood flow in the brain, comprising:

-   -   a) causing currents to flow inside the head by producing        electric fields inside the head;    -   b) measuring at least changes in the electric fields and the        currents; and    -   c) estimating changes in the blood volume of the head, using the        measurements of the electric fields and the currents.

In an embodiment of the invention, using the measurements of electricfields and the currents comprises calculating the impedance of the headat at least two different times.

In an embodiment of the invention, producing electric fields inside thehead comprises placing at least two current-carrying electrodes on thehead and applying at least two different voltages to thecurrent-carrying electrodes.

Optionally, there is more than one current-carrying electrode at thesame voltage.

Optionally, the current-carrying electrodes are sufficiently large inarea so that a significant amount of the current flows through theinterior of the skull, and not through the scalp.

Alternatively or additionally, the electrodes are spread out enough inarea so that a significant amount of the current flows through theinterior of the skull, and not through the scalp.

In an embodiment of the invention, measuring the electric fieldscomprises placing at least two voltage-measuring electrodes on the head,on a separate circuit from the current-carrying electrodes, andmeasuring the voltage difference between the voltage-carryingelectrodes.

Optionally, placing the voltage-measuring electrodes on the headcomprises placing them inside the ears.

Optionally, placing the current-carrying electrodes on the headcomprises placing at least three current-carrying electrodes on thehead, and applying different voltages to the current-carrying electrodescomprises applying at least three different voltages to thecurrent-carrying electrodes so that a desired current distribution isproduced in the head.

Optionally, the desired current distribution is concentrated in adesired region of the brain, and estimating the blood flow in the braincomprises estimating the blood flow in the desired region of the brain.

In an embodiment of the invention, producing electric fields inside thehead comprises:

-   -   a) placing at least one induction coil adjacent to the head; and    -   b) running time-varying current through said at least one        induction coils;        thereby inducing the electric fields inside the head, whereby        causing currents to flow inside the head comprises causing eddy        currents to flow inside the head.

Optionally, the frequency distribution of the time-varying currentrunning through the at least one induction coils is such that the eddycurrents flowing in the head do not reduce the magnetic field at anypoint in the head by more than a factor of 3.

In an embodiment of the invention, measuring the currents inside thehead comprises measuring the magnetic field produced by the eddycurrents.

Optionally, measuring the magnetic field produced by the eddy currentscomprises:

-   -   a) placing two voltage-measuring electrodes on the head;    -   b) measuring the induced electric field by measuring the voltage        difference between the voltage-measuring electrodes; and    -   c) subtracting the part of the electric field induced by the        magnetic field produced by the currents running in the at least        one induction coils, thereby finding the part of the electric        field induced by the magnetic field produced by the eddy        currents.

In an embodiment of the invention, the method also comprises usingphotoplethysmography on tissue inside the head.

Optionally, the tissue is inside the ear.

Alternatively or additionally, the tissue is inside the nose.

In an embodiment of the invention, the method is used to monitor theblood flow in a patient's brain during surgery.

Alternatively, the method is used to monitor the blood flow in apatient's brain during CPR, to verify that the CPR is being performedeffectively.

Alternatively, the method is used to monitor the blood flow in the brainof a patient with a medical condition likely to lead to loss of bloodflow to the brain.

There is thus also provided, in accordance with an embodiment of theinvention, an apparatus for estimating blood flow to the brain,comprising:

-   -   a) a power supply;    -   b) an electric field source which uses the power supply to        produce an electric field in the head, at a safe amplitude and        frequency, thereby producing a current in the head;    -   c) an electrical element which determines at least changes in        the electric field in the head and at least changes in the        current in the head, having sufficient precision to at least        estimate changes in the impedance of the head; and    -   d) a monitor which displays at least information telling a user        when changes in the impedance of the head show a significant        change in blood flow rate.

In an embodiment of the invention, the electric field source comprisesat least two current-carrying electrodes, adapted for forming a goodelectrical connection to the head, and connected to the power supply,and the electrical element comprises:

-   -   a) a controller in the power supply which controls one of the        output voltage and the output current of the power supply, or a        combination of the output voltage and output current; and    -   b) a meter which measures one of voltage across the head,        current through the head, or a combination of voltage across the        head and current through the head which is not controlled by the        controller.

Optionally, the controller in the power supply controls the outputcurrent, and the meter is a voltmeter, and there are twovoltage-measuring electrodes, connected to the voltmeter, whichvoltage-measuring electrodes are adapted for forming a good electricalconnection to the head.

Optionally, the current-carrying electrodes comprise at least threecurrent-carrying electrodes, and at least two of the current-carryingelectrodes are connected in parallel to the same voltage.

Optionally, the current-carrying electrodes are collectivelysufficiently large in area so that a significant amount of the currentflows through the interior of the skull, and not through the scalp.

Alternatively or additionally, the current-carrying electrodes arecollectively sufficiently spread out in area so that a significantamount of the current flows through the interior of the skull, and notthrough the scalp.

In an embodiment of the invention, the voltage-measuring electrodes areadapted to be placed inside an opening in the head.

Optionally, the voltage-measuring electrodes are adapted to be placedinside the ears.

Optionally, the voltage-measuring electrodes are conical and padded,thereby allowing them to be pressed firmly enough into the ears to makegood electrical contact, without damaging the ear drums.

Optionally, there is also a probe adapted for measuring blood flowphotoplethysmographically in the ears, which probe is combined with thevoltage-measuring electrodes.

In an embodiment of the invention, the at least two current-carryingelectrodes comprise at least three current-carrying electrodes, and thepower supply is capable of simultaneously applying at least threedifferent voltages to the current-carrying electrodes, whereby a desiredcurrent distribution is produced inside the head.

Optionally, the current-carrying electrodes are adapted to be placed inlocations on the head such that the desired current distribution isconcentrated in a desired region of the brain.

In an embodiment of the invention:

-   -   a) the power supply produces a time-varying power supply        current;    -   b) the means for producing an electric field in the head        comprises at least one induction coil, connected to the power        supply, which induces an electric field in the head by producing        a time-varying magnetic field in the head, the current in the        head thereby being an eddy current;    -   c) the means for determining at least changes in the electric        field in the head comprises a controller in the power supply,        which determines the rate of change of the power supply current,        and thereby determines the rate of change of the magnetic field        in the head, and the induced electric field in the head; and    -   d) the means for determining at least changes in the current in        the head comprises a sensor which senses the magnetic field        produced by the current in the head.

Optionally, the power supply is capable of operating over at least partof the range between 10 kHz and 100 kHz.

Alternatively or additionally, the power supply is capable of operatingover at least part of the range between 100 kHz and 1 MHz.

Alternatively or additionally, the power supply is capable of operatingover at least part of the range between 1 MHz and 10 MHz.

Alternatively or additionally, the power supply is capable of operatingover at least part of the range between 10 MHz and 100 MHz.

In an embodiment of the invention, the sensor comprises at least one ofthe at least one induction coils.

Alternatively or additionally, the sensor comprises a separate sensingcoil which measures the voltage induced by changes in magnetic fluxpassing through it.

Alternatively or additionally, the sensor comprises a solid-statemagnetic field sensor.

Alternatively or additionally, the sensor comprises voltage-measuringelectrodes which measure an electric field induced by the time-varyingmagnetic field produced by the at least one induction coil.

In an embodiment of the invention, there is also a photoplethysmographicblood-flow measuring probe, sized and shaped to be placed in the ears.

Optionally, the probe is sufficiently wide at its base that it cannotdamage the eardrum when inserted into the ears.

Optionally, the probe is surrounded by a holding element which, wheninserted into the ear, holds the probe in a position and orientation toallow repeated optical measurements of the same location.

In an embodiment of the invention, the apparatus is portable enough foruse in the field by emergency medical technicians.

In an embodiment of the invention, there is also:

-   -   a) a head motion sensor; and    -   b) a controller which uses data from the head motion sensor to        reduce motion artifacts in estimating the blood flow.

There is also provided in accordance with an exemplary embodiment of theinvention, apparatus for estimating blood flow to the brain, comprising:

(a) an impedance measurement system including at least one electrode andwhich generates at least one impedance measurement; and

(b) a monitor which determines changes in blood flow to the brain basedon said at least one measurement,

wherein said at least one electrode is configured to cause a significantamount of at least 1% of an output current of the measurement system toflow through the interior of the skull and not through the scalp.Optionally, said amount is at least 10%. Optionally, said amount is atleast 30%.

In an exemplary embodiment of the invention, the smallest convex area onthe surface of the head that includes every current-carrying electrodeof a same polarity is at least 1 cm across.

In an exemplary embodiment of the invention, the apparatus comprises:

-   -   i) a power supply comprising a controller which controls an        output current of the power supply;    -   ii) at least two current-carrying electrodes, adapted for        forming a good electrical connection to the head, and connected        to the power supply, which use the power supply to produce an        electric field in the head, at a safe amplitude and frequency,        thereby causing the output current to flow in the head; and    -   iii) a voltmeter, and two voltage-measuring electrodes connected        to the voltmeter, which voltage-measuring electrodes are adapted        for funning a good electrical connection to the head, thereby        allowing the voltmeter to determine at least changes in the        electric field in the head, having sufficient precision to at        least estimate changes in the impedance of the head,

wherein said monitor displays at least information telling a user whenchanges in the impedance of the head show a significant change in bloodflow rate. Alternatively or additionally, said area is at least 2 cmacross. Optionally, said area is at least 5 cm across. Optionally, saidarea is at least 10 cm across.

In an exemplary embodiment of the invention, at least a portion of onecurrent-carrying electrode is adjacent on two opposite sides to twoportions of a same voltage-measuring electrode, or at least a portion ofone voltage-measuring electrode is adjacent on two opposite sides to twoportions of a same current-carrying electrode, or both.

In an exemplary embodiment of the invention, at least a portion of onecurrent-carrying electrode is adjacent on two opposite sides to twoportions of a same voltage-measuring electrode, or at least a portion ofone voltage-measuring electrode is adjacent on two opposite sides to twoportions of a same current-carrying electrode, or both.

In an exemplary embodiment of the invention, at least a portion of onecurrent-carrying electrode is adjacent on two opposite sides to twoportions of the same voltage-measuring electrode.

In an exemplary embodiment of the invention, at least a portion of onevoltage-measuring electrode is adjacent on two opposite sides to twoportions of the same current-carrying electrode.

In an exemplary embodiment of the invention, at least one of saidelectrodes comprises as annular-shaped electrode that surrounds theelectrode or the portion of the electrode that said annular-shapedelectrode is adjacent to.

In an exemplary embodiment of the invention, at least portions of thevoltage-measuring electrode and the current-carrying electrode formintertwined spirals.

In an exemplary embodiment of the invention, at least one electrode isadapted to be placed inside an opening in the head, near an opening inthe skull, or near a thin region of the skull.

In an exemplary embodiment of the invention, the apparatus comprises:

-   -   a) a power supply comprising a controller which controls an        output current of the power supply;    -   b) at least two current-carrying electrodes, adapted for forming        a good electrical connection to the head, and connected to the        power supply, which use the power supply to produce an electric        field in the head, at a safe amplitude and frequency, thereby        causing the output current to flow in the head; and    -   c) a voltmeter, and two voltage-measuring electrodes connected        to the voltmeter, which voltage-measuring electrodes are adapted        for forming a good electrical connection to the head, thereby        allowing the voltmeter to determine at least changes in the        electric field in the head, having sufficient precision to at        least estimate changes in the impedance of the head.

In an exemplary embodiment of the invention, the voltage-measuringelectrodes are adapted to be placed inside an opening in the head.Optionally, the voltage-measuring electrodes are adapted to be placedinside the ears. Optionally, the voltage-measuring electrodes areconical and padded, thereby allowing them to be pressed firmly enoughinto the ears to make good electrical contact, without damaging the eardrums. Alternatively or additionally, the apparatus including a probeadapted for measuring blood flow photoplethysmographically in the ears,which probe is combined with the voltage-measuring electrodes.

In an exemplary embodiment of the invention, at least one electrode isadapted by its size and shape to be placed near an opening of the skull.Optionally, the opening is an eye socket, and the electrode is shaped tofit over a closed eyelid.

In an exemplary embodiment of the invention, the opening is the foramenmagnum, and the electrode is shaped to fit near the base of the skull.

In an exemplary embodiment of the invention, the opening is an ear, andthe electrode is sized and shaped to be placed in the ear canal.

In an exemplary embodiment of the invention, the opening is an ear, andthe electrode is sized and shaped to be placed behind the ear.

In an exemplary embodiment of the invention, at least one electrode isadapted by its size and shape to be placed near a thin region of theskull. Optionally, the thin region is the temple.

In an exemplary embodiment of the invention, the apparatus comprises:

-   -   a) a power supply comprising a controller which controls an        output current of the power supply;    -   b) at least two current-carrying electrodes, adapted for forming        a good electrical connection to the head, and connected to the        power supply, which use the power supply to produce an electric        field in the head, at a safe amplitude and frequency, thereby        causing the output current to flow in the head; and    -   c) a voltmeter, and two voltage-measuring electrodes connected        to the voltmeter, which voltage-measuring electrodes are adapted        for forming a good electrical connection to the head, thereby        allowing the voltmeter to determine at least changes in the        electric field in the head, having sufficient precision to at        least estimate changes in the impedance of the head;    -   wherein the current-carrying electrodes are collectively        sufficiently spread out in area so that a significant amount of        at least 1% of the current flows through the interior of the        skull, and not through the scalp, and wherein the at least two        current-carrying electrodes comprise at least three        current-carrying electrodes, and the power supply is capable of        simultaneously applying at least three different voltages to the        current-carrying electrodes, whereby a desired current        distribution is produced inside the head.

Optionally, the current-carrying electrodes are adapted to be placed inlocations on the head such that the desired current distribution isconcentrated in a desired region of the brain.

There is also provided in accordance with an exemplary embodiment of theinvention, apparatus for estimating blood flow to a brain, comprising:

(a) an impedance measurement system including at least one electrode andwhich generates at least one impedance measurement; and

(b) a monitor which determines changes in blood flow to the brain basedon said at least one measurement,

wherein the at least one electrode is adapted by one or both of theirsize and shape to be used for children.

Optionally, said system comprises:

-   -   i) a power supply comprising a controller which controls an        output current of the power supply;    -   ii) at least two current-carrying electrodes, adapted for        forming a good electrical connection to the head, and connected        to the power supply, which use the power supply to produce an        electric field in the head, at a safe amplitude and frequency,        thereby causing the output current to flow in the head; and    -   iii) a voltmeter, and two voltage-measuring electrodes connected        to the voltmeter, which voltage-measuring electrodes are adapted        for forming a good electrical connection to the head, thereby        allowing the voltmeter to determine at least changes in the        electric field in the head, having sufficient precision to at        least estimate changes in the impedance of the head,    -   wherein said monitor displays at least information telling a        user when changes in the impedance of the head show a        significant change in blood flow rate.

In an exemplary embodiment of the invention, the electrodes are adaptedby one or both of their size and shape to be used for newborn babies.

In an exemplary embodiment of the invention, the electrodes are adaptedby one or both of their size and shape to be used for premature babies.

In an exemplary embodiment of the invention, the distance between twodifferent electrodes of said at least one electrode, or different armsof one electrode, is between 1 mm and 2 mm, thereby adapting theapparatus to be used in a patient whose scalp is between 1 mm and 2 mmthick.

In an exemplary embodiment of the invention, the distance between twodifferent electrodes of said at least one electrode, or betweendifferent arms of one electrode, is between 2 mm and 5 mm thick, therebyadapting the apparatus to be used in a patient whose scalp plus skull isa total of between 2 mm and 5 mm thick.

In an exemplary embodiment of the invention, the at least one electrodeis adapted to be used in a patient whose scalp is between 1 mm and 2 mmthick.

In an exemplary embodiment of the invention, the at least one electrodesis adapted to be used in a patient whose scalp plus skull is a total ofbetween 2 mm and 5 mm thick.

There is also provided in accordance with an exemplary embodiment of theinvention, apparatus for estimating blood flow to the brain, comprising:

-   -   a) a power supply comprising a controller which controls an        output current of the power supply;    -   b) at least two current-carrying electrodes, adapted for forming        a good electrical connection to the head, and connected to the        power supply, which use the power supply to produce an electric        field in the head, at a safe amplitude and frequency, thereby        causing the output current to flow in the head;    -   c) a voltmeter, and two voltage-measuring electrodes connected        to the voltmeter, which voltage-measuring electrodes are adapted        for forming a good electrical connection to the head, thereby        allowing the voltmeter to determine at least changes in the        electric field in the head, having sufficient precision to at        least estimate changes in the impedance of the head;    -   d) at least one electrode structure to which at least one        current-carrying electrode and at least one voltage-measuring        electrode are mechanically connected; and    -   e) a monitor which generates a signal indicating a significant        change in blood flow rate, based on said measuring.

Optionally, said connection is non-elastic. Alternatively saidconnection is rigid.

There is also provided in accordance with an exemplary embodiment of theinvention, a method of estimating blood flow in the brain of a patient,comprising:

-   -   a) causing currents to flow inside the head by placing at least        two current-carrying electrodes on the head and applying at        least two different voltages to the current-carrying electrodes,        thereby producing electric fields inside the head;    -   b) measuring at least changes in the electric fields and the        currents; and    -   c) estimating changes in the blood volume of the head, using the        measurements of the electric fields and the currents, wherein        the patient's scalp is between 1 and 2 mm thick or wherein the        total thickness of the patient's scalp plus skull is between 2        and 5 mm.

There is also provided in accordance with an exemplary embodiment of theinvention, a method of estimating blood flow in the brain, comprising:

-   -   a) causing currents to flow inside the head by placing at least        two current-carrying electrodes on the head, at least one of        them adjacent to an opening or thin area in the skull, and        applying at least two different voltages to the current-carrying        electrodes, thereby producing electric fields inside the head;    -   b) measuring at least changes in the electric fields and the        currents; and    -   c) estimating changes in the blood volume of the head, using the        measurements of the electric fields and the currents.        Optionally, at least one electrode is placed at an opening.

There is also provided in accordance with an exemplary embodiment of theinvention, a method of estimating blood flow in the brain, comprising:

-   -   a) causing currents to flow inside the head by placing at least        two current-carrying electrodes on the head and applying at        least two different voltages to the current-carrying electrodes,        thereby producing electric fields inside the head;    -   b) measuring at least changes in the electric fields and the        currents; and    -   c) estimating changes in the blood volume of the head, using the        measurements of the electric fields and the currents,    -   wherein the smallest convex area on the surface of the head        which includes every current-carrying electrode of a given        polarity is at least 2 cm across.

BRIEF DESCRIPTION OF THE DRAWINGS

Exemplary embodiments of the invention are described in the followingsections with reference to the drawings. The drawings are generally notto scale and the same or similar reference numbers are used for the sameor related features on different drawings.

FIG. 1A is a schematic cross-sectional view of a head with electrodes,according to an exemplary embodiment of the invention;

FIGS. 1B, 1C, and 1D are drawings of the surface of an electrodestructure, which surface is to be placed facing the skin, according tothree other exemplary embodiments of the invention;

FIG. 2A is a schematic plot of typical impedance data according to thesame or a different exemplary embodiment of the invention than thoseshown in FIGS. 1A-1D;

FIG. 2B is a schematic cross-sectional view showing an electrode and anoptical probe inserted into an ear;

FIGS. 3A, 3B, and 3C are schematic perspective views of a head withinduction coils according to three other exemplary embodiments of theinvention;

FIG. 4 is a schematic view of the head showing the brain and inductioncoils, according to the same embodiment of the invention as FIG. 3B; and

FIGS. 5A, 5B, and 6 are perspective views of a head with electrodes, anda monitor, according to three different exemplary embodiments of theinvention.

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS

FIG. 1 shows a cross-section of a head 100 seen from the top, includinga skull 102 with two openings 104 associated with the ears, and aninterior region 106 which includes the brain. It is desired to measurechanges in the electrical impedance of interior region 106, withouthaving the measurements dominated by the much greater impedance of theskull. Two positive current-carrying electrodes 108 are shown in contactwith the skin on the right side of the head, one in front of the ear andone behind the ear. Similarly, two negative current-carrying electrodesare shown in contact with the skin on the left side of the head. Thismay be varied, for example there is only one electrode on each side, orthere are more than two electrodes on each side, or the electrodes areabove or below the ears, or on the ears, and the number of positiveelectrodes need not equal the number of negative electrodes. Having alarge area of the cranium, for example 2% or 5% or 10% or more of thesurface of the head, covered by electrodes, keeps a significant amountof the current flowing through the interior of the head, and reduces theamount of current that bypasses the interior of the head by flowingthrough the scalp. This is facilitated by having more than one electrodeon each side, or by having large electrodes, which conform or can bemade to conform to the curvature of the head. Optionally, instead ofhaving one large electrode on each side of the head, or several smallelectrodes at the same voltage on each side covering a large total area,there is, on at least one side of the head, an annular electrode with awide diameter, even if it has a thin annnlus with a small total area.Optionally, there is also an electrode, not necessarily large, in thecenter of the annular electrode, with the same voltage, and optionallythe annulus has one or more breaks in it. Alternatively or additionally,there are a plurality of electrodes spread out over a large area, withthe same voltage, even if the total area of the electrodes themselves issmall. The current will tend to be focused to go through the interior ofthe head, rather than through the scalp, as if the whole area inside theannular electrode, or the whole area covered by the spread outdistribution of electrodes, were one large electrode. All of theseoptions can be used on either one or both sides of the head.

Optionally, the electrode configuration causes at least 90% of thecurrent to go through the interior of the head. Alternatively, at least50% of the current goes through the interior of the head, or at least20%, or at least 10%, or at least 1%. Having a significant amount ofcurrent going through the interior of the head means having enoughcurrent going through the interior of the head so that the impedancemeasurements are sufficiently dependent on blood volume that they can beused to measure the blood flow.

Optionally, electrodes 108 and 110 are kept in good electrical contactwith the skin by a conductive gel, such as those used in ECGmeasurements.

A constant current is driven from electrodes 108 to electrodes 110 bypower supply 112. Alternatively power supply 112 produces a constantvoltage, or some combination of constant voltage and constant current,but the current is measured. Optionally, different electrodes, even onthe same side of the head, have different voltages applied to them bythe power supply, in order to produce a desired distribution of currentflowing through the head. For example, current could be concentrated inone region of the brain, to measure blood flow in that region, orcurrent could be distributed uniformly to measure global blood flow.Optionally, the current density is more than twice as great in oneregion of the brain than it is in other regions. Alternatively, thecurrent density is 50% greater, or 20% greater, or 10% greater, in oneregion of the brain than in other regions. The current distribution inthe brain produced by different shapes, sizes, locations and voltages ofelectrodes are optionally evaluated using finite element analysissoftware, or any other numerical or analytic method known to the art.

Although the foregoing description, and the arrow shown in power supply112, suggest that DC current is applied to the head, in practice, forsafety reasons, AC current is generally applied, optionally atfrequencies between 20 and 100 kHz, and the “positive” and “negative”electrodes 108 and 110 in FIG. 1 really represent two different phasesof the AC voltage applied by the power supply, 180 degrees apart.Optionally, there are three or more electrodes to which three or moredifferent phases of AC voltage are applied. For safety reasons, and toavoid nerve stimulation, the current is optionally limited, for exampleto 0.5 milliamperes or 1 milliampere, depending to some extent on thearea and location of the electrodes. This is a potential advantage ofusing a constant current rather than a constant voltage power supply.Optionally, the current is not too much lower than this, for example notless than 0.1 milliampere, since the impedance measurement may be lessaccurate at lower current. Optionally, the current is applied atfrequencies between 20 and 40 kHz, which is high enough to run themaximum current safely, but is still low enough so that the current islargely confined to the blood and other extracellular fluid, and isexcluded from the interiors of cells by the high resistance cellmembranes. This makes the measured impedance maximally sensitive toblood volume.

Optionally, the current is run between 70 and 100 kHz, instead of or inaddition to 20 to 40 kHz. In the higher frequency range, the cellmembranes may already begin to short out due to their finitecapacitance, and a significant amount of the current may flow inside thecells, as well as in the blood and extracellular fluid. Although theimpedance may be somewhat less sensitive to changes in blood volume inthe higher frequency range, the spatial distribution of current may bedifferent than at lower frequency, due to the inhomogeneous distributionof blood and extracellular fluid throughout the brain. Obtainingimpedance data at high frequency, especially if it supplements dataobtained at lower frequency, may provide additional data about thedistribution of blood flow in the brain, or the distribution of pooledblood from a cerebral hemorrhage, for example. Optionally, the currentis also run at intermediate frequencies, 40 to 70 kHz, to provideadditional data on blood distribution, or is only run at intermediatefrequencies.

In an exemplary embodiment, voltage-measuring electrodes 114 areinserted into the ears through openings 104, reaching locations that arerelatively well connected electrically with the interior of the skull,and measure the voltage across the interior of the head associated withthe current flowing between current-carrying electrodes 108 and 110.Optionally, electrodes 114 are conical Ag/AgCl electrodes padded with asponge soaked in a conductive gel. The conical shape prevents theelectrodes from pressing against and possibly damaging the ear drums,when they are pushed with some force into the ear canals in order tomake good electrical contact. Alternatively, electrodes 114 are shapedlike the ear canal, similar to hearing aids, or are soft enough so thatthey conform to the shape of the ear canal, but making the electrodesrelatively rigid has the potential advantage that they may stay incontact with the skin better. Optionally, the ear canal betweenelectrodes 114 and the ear drum is completely or partially filled with aconductive gel, or another conducting fluid-like material. Optionally,there are also voltage-measuring electrodes placed just behind the ear,which are shorted to the voltage-measuring electrodes placed in the earcanal, to provide a greater total electrode area, and to spread out theelectrode area more. Electrodes 114 are attached to a high impedancerecording device 116, so very little current flows through electrodes114. This means that the voltage measured by recording device 116depends mostly on the voltage drop across the interior of the headproduced by power supply 112, and does not depend very much on theimpedance of the skull, or on the impedance associated with the contactbetween electrodes 114 and the head, or between electrodes 108 or 110and the head. If the voltage were instead measured between electrodes108 and 110, then the voltage might be dominated by the skull, or by thecontact between the electrodes and the skin. Alternatively, electrodes114 are not placed inside the ears, but on the surface of the head. Evenin this case, depending on the dimensions and placement of electrodes108, 110 and 114, and on the thickness of the skull, the voltagemeasured by recording device 116 is not sensitive to the voltage dropacross the skull, or at least is less sensitive to the voltage dropacross the skull than if the voltage were measured between electrodes108 and 110, and the voltage measured by recording device 116 issufficiently sensitive to the impedance of the interior of the head thatchanges in blood volume can be detected. In particular, if the diameterof the current-carrying electrodes, and the distance from thecurrent-carrying electrodes to the voltage-measuring electrodes, is atleast a few times greater than the thickness of the skull, then thepotential of the voltage-measuring electrodes will tend to besubstantially closer to the potential of the brain surface than to thepotential of the current-carrying electrodes, on that side of the head.In some embodiments, electrodes 114 are placed on the temples, where theskull is thinner than at most other parts of the head, in order to makethe voltage measured by recording device 116 less dependent on the skullimpedance, and more sensitive to the impedance of the interior of thehead. In other exemplary embodiments, voltage-measuring electrodes 114,or current-carrying electrodes 118 and 110, or both, are placed on thetemples, or over the eye sockets, for example over the eyelids when theeyes are closed, or at the base of the skull near the foramen magnum, orover any combination of these locations.

In an exemplary embodiment of the invention, as shown in FIG. 1B, thecurrent-carrying electrode and voltage-measuring electrode on one sideof the head are part of a single electrode structure 117, for example inthe shape of a flat disk. In one example, an annular current-carryingelectrode 118 surrounds a central voltage-measuring electrode 120,separated from it by an annular insulating region. FIG. 1B shows theface of electrode structure 117 which is in contact with the skin. Therelatively broad spread of the current-carrying electrode allows morecurrent to go through the high impedance of the skull into the lowresistance of the brain, while less current travels through the lowimpedance vascularized layer of the scalp, where it might bypass theskull and brain. To the extent that the diameter of the current-carryingelectrode is comparable to the thickness of the scalp and skull, or atleast comparable to the thickness of the scalp, the voltage-measuringelectrode will tend to be relatively insensitive to the large voltagedrop across the high resistance epidermis and skull, and relatively moresensitive to the voltage drop across the brain. For example, electrodestructure 117 is 1 cm in diameter, or 2 cm in diameter, or 5 cm indiameter. The voltage-measuring and current-carrying electrodes haveproportional dimensions similar to those shown in FIG. 1B, oralternatively have different dimensions. In an exemplary embodiment ofthe invention, the other side of the disk has separate contact points,connected respectively to the current-carrying and voltage-measuringelectrodes, suitable for attaching electrical leads, which are connectedin turn to power supply 112 and recording device 116. Alternatively,integral lead wires are provided. Optionally, electrode structures likethat shown in FIG. 1B are used on both sides of the head.

In an alternative embodiment, instead of electrode structure 117,electrode structure 122, shown in FIG. 1C, is used. There is an annular(optionally, a ring with a gap) current-carrying electrode 118, and acentral voltage-measuring electrode 120, as in electrode structure 117,but there is a second voltage-measuring electrode 124, outsidecurrent-carrying electrode 118, and optionally electrically shorted tocentral voltage-measuring electrode 120. Electrode structure 122 is, forexample, 1 cm in diameter, or 2 cm, or 5 cm, or has a smaller or largerdiameter. The relative proportions of the electrodes need not be thesame as the exemplary proportions shown in FIG. 1C. The broader spreadof the voltage-measuring electrode, compared to electrode structure 117,may make the voltage measurement even less sensitive to the voltage dropacross the epidermis and skull. Furthermore, the broad spread of thevoltage-measuring electrode, which is at a constant potential, may tendto reduce radial electric fields and radial currents in the scalp, andcause a greater portion of the current to flow through the interior ofthe head, similar to the effect of a broadly spread out current-carryingelectrode.

In an alternative embodiment, an electrode structure 126, shown in FIG.1D, is used. This structure has a spiral shaped current-carryingelectrode 128 intertwined with a spiral shaped voltage-measuringelectrode 130. Depending on the details of the geometry, electrodestructure 126 potentially provides a greater surface area for thecurrent-carrying electrode than electrode structures 117 or 122, therebyproviding a more focused pattern of current flow through the interior ofthe head, and making better use of the available surface area. Thegreater surface area for voltage-measuring electrode 130 may providesimilar benefits. As long as the widths of the different arms of theelectrodes, and the spacing between them, are at least comparable to thethickness of the scalp and/or the skull, the voltage-measuringelectrodes will tend to be relatively insensitive to the voltage drop inthe scalp and/or the skull, as well as to any voltage drop between thecurrent-carrying electrodes and the skin, due to poor contact, and willbe relatively more sensitive to the voltage drop across the brain. Forexample, adjacent turns of the spirals is FIG. 1D are spaced 1 mm apart,or 2 mm, or 5 mm, and electrode structure 126 has a diameter of 1 cm, or2 cm, or 5 cm. Electrode structures with a variety of geometricconfigurations, which meet these criteria, may provide benefits similarto those provided by one or more of electrode structures 117, 122, and126.

Optionally, any combination of electrode structures 117, 122 and 126 isused, as well as separate current-carrying and voltage-measuringelectrodes as shown, for example, in FIG. 1A. Optionally, more than twoelectrode structures are placed on the head, but, optionally, only twoof them are used at a time to produce current and measure voltage. Thesetwo electrode structures, or separate sets of electrodes, need not beplaced symmetrically on opposite sides of the head, but, for example,one could be placed over an eye socket, and one near an ear. Placing theelectrode structures in different locations may give information aboutthe impedance in different regions of the head. When electrodes areplaced over an eye socket, the eye is preferably closed, for examplebecause the patient is unconscious, and the electrodes are placed overthe eyelid.

Optionally, electrode structures such as those shown in FIGS. 1B, 1C,and 1D, or separate electrodes such as those shown in FIG. 1A, areplaced over or near openings or thin areas of the skull, for example theears, the eye sockets, the temples, and the foramen magnum. Optionally,the electrode structures or separate electrodes are not rigid flatdisks, but are flexible enough to be molded to fit the shape of the headin those regions, or are relatively rigid but are molded to fit theshape of the head in those regions, optionally with some flexibility toallow them to be adjusted to slightly different head shapes in differentindividuals, with conductive gel used to fill in any small gaps. Thestiffness of the electrode structure, and the manner its which it isattached to the skin, optionally depends on where it is attached. Forexample, a softer electrode structure, exerting less pressure, may beused over the closed eyelids, than is used over the temples, to avoiddiscomfort or damage to the eyes. Optionally, the conductive gel doesnot cover the entire face of the electrode structure, but is appliedonly on and near the electrodes themselves, or only on and near thecurrent-carrying electrodes, so that a current-carrying electrode is notshorted to an adjacent voltage-measuring electrode.

Optionally, the electrodes come in different sizes and/or shapes for useon different people, for example adults and children. Optionally,different people may use the same size and shape of electrode, butdifferent parts of the electrode make good contact with the skin indifferent people.

Dividing the voltage measured by recording device 116 by the currentproduced by power supply 112 gives a measure of the electrical impedanceof interior region 106, which is related to the blood volume in thebrain. Optionally, the voltage produced by power supply 112 is used inaddition to, or instead of, the voltage measured by recording device 116in calculating the impedance, possibly as a check on the reasonablenessof the voltage measured by recording device 116. But often, the voltageproduced by power supply 112 is influenced more by the skull impedance,and less by the impedance of the interior of the head, than the voltagemeasured by recording device 116. If AC current is used, then of coursethe current and voltage are each expressed by a complex number,representing the amplitude and phase. At very high frequencies, forexample above about 100 kHz, the capacitance of the cell membranes willstart to look like a short circuit, and current will flow almost aseasily through the cells as it flows through the blood and other fluidsurrounding the cells. At these high frequencies, the impedance of thehead will be less sensitive to blood volume than it is at lowerfrequencies, because it will depend on the total volume of the brain,including the cells, not just on the volume of the blood and theextracellular fluid. Optionally, for this reason, frequencies belowabout 100 kHz are used to measure the impedance of the head. Optionally,measurements of the relative phase of the voltage measured by recordingdevice 116 or by power supply 112, and the current produced by powersupply 112, particularly at higher frequencies such as 100 kHz, are usedto measure the impedance of the head. Such phase measurements arepotentially useful at frequencies comparable to 100 kHz, where theimpedance of the head has a substantially capacitive component due tothe cell membranes, especially if the capacitive part of the impedanceis insensitive to blood volume, or has a different dependence on bloodvolume than the resistive impedance of the head. Even if the measuredimpedance is affected to a large degree by undesired effects such as theskull impedance, or the capacitance of the cell membranes, the measuredimpedance is still useful for measuring blood volume if it dependssignificantly on blood volume as well.

Optionally, the impedance is never actually calculated, but the bloodvolume is determined directly from the voltage data, particularly if thecurrent produced by power supply 112 is always the same. Alternatively,feedback to the power supply is used to keep the voltage measured byrecording device 116 constant (i.e. constant amplitude and phase), andthe current produced by power supply 112 is used directly to determinethe blood volume. Variants on these methods, for example, keeping somelinear combination of voltage and current the same, will be apparent tothose skilled in the art.

FIG. 2A shows a plot 200 of resistive impedance vs. time, measured asdescribed in FIG. 1, over a period of time covering several pulsecycles. The vertical axis 202 represents impedance, or resistance, andthe horizontal axis 204 represents time. The average resistance R overtime has a value given by level 206 on the vertical, axis, and thevariation in resistance ΔR, associated with the pulse cycle, is shown byinterval 208. The resistance decreases during the systolic phase of thepulse, when the blood volume V of the brain is higher, and increasesduring the diastolic phase when the blood volume V is lower. Therelative change in blood volume over a pulse period ΔV/V is comparableto ΔR/R. If desired, the exact relation between ΔV/V and ΔR/R can becalibrated for a given configuration of electrodes by comparing measuredvalues of ΔR/R with measurements of blood flow performed by other meansknown to the art. The blood flow to the brain is found by multiplyingΔV/V by the total brain blood volume V (estimated, for example, from aknown average value for humans) and the pulse rate.

Even if a calibration is not done, or even if the calibration is notaccurate if applied to a different patient from the calibrated patient,the estimated values of blood flow obtained by this technique are stilladequate for some applications of interest, such as determining whetherCPR is working at all, or detecting a sudden decrease in blood flow tothe brain during surgery. If CPR is not being administered properly, orif blood flow to the brain is reduced by a stroke or another suddenevent suffered during surgery, then the blood flow to the brain may beessentially zero, or much lower than normal, and this may be detectedeven if the technique does not measure absolute values of blood flowvery accurately.

FIG. 2B shows a closeup view of voltage-measuring electrode 114 insertedinto ear canal 104. Electrode 114 is connected to recording device 116,which analyzes the voltage data and displays information about the headimpedance and the blood flow. Electrode 114 is surrounded by a sponge218, soaked in an electrically conducting gel. Electrode 114 is conicalin shape, and too wide at the base to reach the ear drum when it isinserted into the ear. Optionally, there is a system for doing opticalmeasurements of blood flow in the ear, combined with electrode 114. Alight source 220, for example a red or infrared laser or laser diode,sends light through optical fiber 222. Light ray 224 reflects off asurface 226 inside the ear, for example the ear drum, or another surfacewhose color is affected by blood flow and/or oxygenation of the blood.Sponge 218 holds optical fiber 222 firmly enough in place so that if themeasurements are repeated, light ray 224 always reflects fromsubstantially the same place, so any changes in reflectivity are due tochanges in blood flow or oxygenation, rather than due to fiber 222changing its position or orientation. The reflected light goes intoanother optical fiber 228, which carries it to an analyzer 230. Fiber228 is also held firmly in place by sponge 218. Analyzer 230 usesinformation about the reflectivity of surface 226 to measure or estimateblood flow rate, and/or the degree of oxygenation of the blood, andoptionally displays the information. Analyzer 230 and light source 220are optionally based on any existing system of photoplethysmography,known to those skilled in the art. Optionally a fiber optic cable,comprising a plurality of optical fibers, is used instead of opticalfiber 222 and/or optical fiber 228. Optionally, fibers 222 and 228 arebundled together with the wire connecting electrode 114 to recordingdevice 116. Optionally, analyzer 230 is packaged together with recordingdevice 116. Optionally, data from analyzer 230 is combined with datafrom recording device 116, and a single estimate of blood flow isdisplayed, based on the combined data. Optionally, a probe comprisingfibers 222 and 228, and sponge 218 or a similar element to bold theprobe in place, is used for optical measurements in the ears, even ifvoltage-measuring electrodes 114 are not placed in the ears.

A different method of inducing currents in the brain and measuringvoltages is illustrated in FIGS. 3A, 3B, and 3C, which show coils placedaround the head in different orientations, to induce currents in thebrain. Other magnetic induction methods may be used as well, includingdifferent coil configurations, or the use of rotating or oscillatingpermanent magnets or electromagnets to produce time-varying magneticfields in the head. Measuring the induced currents, by measuring theireffects on the induced magnetic and electric fields, gives informationabout the impedance of the brain, and hence the blood volume of thebrain. In FIG. 3A, coils 302, one on each side of the head, have ACcurrent flowing in them, driven by power supply 304, and generate an ACmagnetic field inside the head. The changing magnetic flux induceselectric fields in the head which are parallel to the currents in coils302, but in the opposite direction. The AC magnetic field optionally islarge enough so that the induced electric fields are large enough toproduce measurable effects, as discussed below, but small enough not toproduce peripheral or central nerve stimulation. Optionally, thethreshold for nerve stimulation is increased by using trains of shortpulses, or other methods known to the art, so that higher AC magneticfields can be used. The induced electric fields cause eddy currents toflow in the brain, of an amplitude which depends on the impedance of thebrain. The eddy currents in turn generate their own magnetic field andan associated induced electric field, reducing the magnetic flux insidethe brain. Coils 306 measure a voltage associated with the AC magneticflux produced by coils 302, and this voltage is recorded by recordingdevice 308. The reduction in magnetic flux caused by the eddy currentsflowing in the brain can be detected by recording device 308, since theinduced voltage will be lower, i.e. the mutual inductance between coils302 and coils 306 will be reduced. The eddy currents will also give themutual inductance an imaginary (dissipative) part, which may be easierto detect than the reduction in the real part of the mutual inductance.An estimate of the absolute impedance of the brain may be made byobserving how the mutual inductance of coils 302 and 306 changes withthe frequency of the AC current. Even without making such an absoluteestimate of the impedance of the brain, changes in impedance of thebrain over time, during the pulse cycle, may be detected by observingthe changes in mutual inductance during the pulse cycle.

Optionally, the electric fields induced by coils 302 are measured byelectrodes placed on or in the head, similar to the voltage-measuringelectrodes shown in FIGS. 1A and 2B. The electrodes are shaped andsized, for example, to be placed in the ears or in the nose, or to beplaced on the temples or elsewhere on the head, with electricallyconducting gel. The induced, electric field depends on the impedance ofthe brain, because it is modified by the eddy currents which depend onthe impedance of the brain.

Here are some considerations used in choosing the frequency of the ACcurrent in coils 302. For a brain resistivity of 2 ohm-meters, typicalof body tissue, the magnetic field produced by the eddy currents, whichdepends on the impedance of the brain, will be comparable to themagnetic field produced by the induction coils when the skin depth ofthe brain is comparable to its radius, about 10 cm. This occurs at afrequency of about 50 MHz. At frequencies well above 100 kHz, however,the impedance of the cell membranes may be effectively shorted out, sothat current flows freely inside as well as outside the cells, so theresistivity of the brain is somewhat lower, and eddy currents becomeimportant at about 30 MHz. The impedance of the brain at such highfrequencies is less sensitive to blood volume than it is below 100 kHz,due to the conduction pathway going inside the cells, but the impedanceis still somewhat sensitive to blood volume, since the total volume offluid in the brain, inside and outside cells, still increases when theblood volume increases. Optionally, frequencies of about 10 MHz, or afew tens of MHz, or even about 100 MHz, are used, since the blood volumemay have the greatest effect on eddy currents in this frequency range.At frequencies well above 30 MHz, eddy currents may largely excludemagnetic flux from the interior of the brain, and the mutual inductanceof the coils may be less sensitive to blood volume. Optionally, thefrequencies used are low enough so that the eddy currents do not reducethe magnetic field at any point inside the head by more than a factor of1.5. Alternatively, the eddy currents do not reduce the magnetic fieldby more than a factor of 3, or by more than a factor of 6. Atfrequencies well below 30 MHz, the small change in the real part of themutual inductance might be difficult to detect, but the change in thedissipative part, which is proportional to frequency well below 30 MHz,might be relatively easy to detect, even below 100 kHz, if it is thedominant dissipative term. Optionally, frequencies between a few tens ofkHz, about 100 kHz, or a few hundred kHz are used, since they are easierto work with than frequencies of a few tens of MHz, and may stillprovide sufficient sensitivity to blood volume. Alternatively,frequencies of a few hundred kHz, about 1 MHz, or a few MHz are used,since they may provide the best trade-off between sensitivity and easeof use.

Eddy currents at different frequencies may have different spatialdistributions in the brain, both because of skin effects (differingmostly at frequencies above 1 MHz), and because of the finitecapacitance of cell membranes (differing mostly at frequencies below 1MHz). Eddy currents may also have a different distribution in the brainthan currents produced by electrodes placed on the head. Differentdistributions of current may provide different data about thedistribution of blood in the head, for example in a patient with acerebral hemorrhage where blood can pool locally at one or morelocations. Optionally, eddy currents are induced at more than onefrequency, or both coils and electrodes are used to induce currents inthe brain, in order to obtain more data about the distribution of bloodin the brain.

Optionally, the currents in induction coils 302 are of a magnitude smallenough not to cause peripheral or central nerve stimulation, or to causedeleterious health effects or discomfort from heating of the brain orother body tissues. The maximum safe currents, which depend on thefrequency and duration of the currents, are well known to those skilledin the art, in the field of magnetic resonance imaging for example.Optionally, the currents used are only a few times less than the maximumsafe currents, or even only a few percent less than the maximum safecurrents, and not many times less, in order not to sacrifice precisionof the measurements.

Optionally, instead of using separate coils 306 to detect the inducedvoltage, coils 302 are used to detect the induced voltage, i.e. theself-inductance of coils 302 is used, instead of the mutual inductancebetween coils 302 and 306. However, a possible advantage of using mutualinductance rather than self-inductance is that the voltage in coils 306will not be sensitive to the resistance of coils 302, or the resistanceof coils 306 if recording device 308 has a high impedance. Inparticular, the dissipative part of the mutual inductance may be thedominant dissipative term in the voltage measured the recording device308, making it easy to measure. On the other hand, if self-inductance ofcoils 302 were used, the dissipative part of the inductance would likelybe small compared to the resistance of the coils, and difficult tomeasure.

Alternatively or additionally, the magnetic fields produced by the coilcurrents and by the eddy currents in the brain are measured by magneticsensors such as Hall sensors, flux gate magnetometers, or SQUIDs. Suchmagnetic sensors will give more local magnetic field measurements thanlarge coils encircling the head, and may give data that is weightedtoward local changes in blood flow, possibly complementing the moreglobal data from large coils. Global data is also optionally obtained byaveraging the results from several local magnetic sensors.

FIG. 3A shows two coils 302 on the sides of the head, and two coils 306,near the midplane of the head, but going around opposite sides of theneck. However, the coils need not be arranged symmetrically as shown.Optionally, there is only one coil 302, or only one coil 306.Optionally, coils 302 are close to the midplane of the head, and coils306 are located on the sides of the head. An optimal configuration ofcoils can optionally be found by using magnetic finite element methods,or other numerical or analytic methods known to the art.

FIGS. 3B and 3C show coils 302 and 306 oriented in other directions withrespect to the head. In addition to obtaining adequate mutual inductancebetween the coils, and adequate dependence of the mutual inductance onthe impedance of the brain, another consideration in choosing the coilorientation is the ability to keep the coils positioned rigidly withrespect to the head. Changes in position of the coils will affect theirmutual inductance and self-inductance, and may appear as spuriouschanges in calculated brain impedance.

FIG. 4 shows coils 402 arranged in front and back of a head, as in FIG.3B, and a coil 406 going around the head from to top to under the chin,to measure the flux induced by coils 402. The brain 410 is shown insidethe head. When currents 412 in coils 402 are flowing in one direction,induced eddy currents 414 flow in the brain in the opposite direction,but the two currents are less than 180° out of phase. (Similar inducededdy currents in the brain would also be seen with the coilconfigurations shown in FIG. 3A or 3C, but the currents would be flowingin different directions, generally opposite to the currents flowing inthe coils.) Currents 414 reduce the magnetic flux inside the brain, andreduce the total flux passing through coils 402 and 406. Currents 414also change the phase of the flux passing through coils 402 and 406,relative to the phase of current 412 in coils 402. This change inamplitude and phase of the flux is detected by coil 406 as a change inthe amplitude and phase of the voltage of coil 406, relative to theamplitude and phase of current 412. Thus the amplitude and phase of thevoltage in coil 406 provides information about the impedance of brain410.

Optionally, a C-shaped element of high magnetic permeability, not shownin the drawings, extends between the two coils 302 in any of FIG. 3A,3B, or 3C, in order to increase the magnetic field induced in the brain,for a given current in coils 302. This would reduce the size and cost ofthe required power supply, and reduce the ohmic heating of the coils, toproduce a given magnetic field and induced electric field in the brain.Such a C-shaped element could, however, have the potential disadvantageof introducing an additional source of dissipation, due to eddy currentsand hysteresis in the magnetic material, that might make it moredifficult to detect the eddy currents introduced in the brain by coils302, and many high permeability alloys have lower permeability at highfrequencies, especially above 1 MHz. Optionally the C-shaped element islaminated, to reduce eddy currents and increase the effectivepermeability at a given frequency. Optionally, the C-shaped element ismade of vanadium permendur, or a similar alloy with low magneticanisotropy, because its permeability may not fall off as much at highfrequencies as is the case with other high permeability materials.

FIGS. 5A and 5B illustrate portable embodiments of the invention thatare potentially suitable for use in the field, in contrast tonon-portable embodiments of the invention that are suitable for use in ahospital setting during surgery, for example. Assemblies 502 containboth current-carrying and voltage-measuring electrodes, either placed onthe temples, as in FIG. 5A, or on the ears, and with thevoltage-measuring electrodes optionally inserted into the ears, as inFIG. 5B. Optionally, assembly 502 on each side of the head covers theears, resembling earmuffs, with current-carrying electrodes outside theears and voltage-measuring electrodes inside the ears. Optionally, thereis more than one current-carrying electrode on each side. Optionally,some of the electrodes are placed on the temples or elsewhere on thehead, and some of them are placed on or in the ears.

Alternatively or additionally, assemblies 502 contain coils which induceeddy currents in the brain, and coils or other magnetic sensors whichdetect the eddy currents. Optionally, if assemblies 502 contain coils,they are substantially bigger than shown in FIGS. 5A and 5B, in order toproduce a magnetic field that is more uniform in the brain, rather thanconcentrated near the assemblies, and in order to reduce the ohmic powergenerated by the coils when producing a given magnetic field.Alternatively, the coils are small, and are inserted into the ears,particularly for making local measurements of impedance near the ears.

Monitor 504 optionally displays the blood volume or blood flow rate as afunction of time, determined from the impedance measurements.Alternatively or additionally, monitor 504 has warning lights, forexample a green light which lights up when the blood flow rate to thebrain is satisfactory, and a red light which lights up, and/or a buzzerwhich sounds, when the blood flow rate is too low, or changes suddenly.Optionally, monitor 504 has five or fewer warning lights, to minimizethe information that an emergency medical technician has to siftthrough, when looking at the monitor.

Optionally, a power supply is packaged together with monitor 504.Alternatively, there is a separate power supply, not shown in FIGS. 5Aand 5B.

FIG. 6 shows a similar embodiment of the invention, but with monitor 504mounted on the patient's forehead. Alternatively, there are twomonitors, one mounted on the patient's forehead which, for example, hasonly a few warning lights, and one not mounted on the patient whichdisplays more information.

Optionally, any of recording device 116 in FIGS. 1A and 2B, power supply112 in FIG. 1A, analyzer 230 in FIG. 2B, power supply 304 in FIGS. 3A,3B, and 3C, recording device 308 in FIGS. 3A, 3B and 3C, and monitor 504in FIGS. 5A, 5B and 6, comprise a controller, which controls thecurrents sent to the current-carrying electrodes or coils, and analyzesthe data. Optionally, the controller includes any of a CPU, powerelectronics, an AC/DC converter, and non-volatile memory to storesoftware and data. Optionally, different elements of the controller arelocated in different places, for example the power supply and therecording device, and/or the controller or parts of the controller arepackaged separately.

These portable versions could be used, for example, during theadministration of CPR by emergency medical technicians, to monitorwhether the CPR is being administered effectively. Studies (for example,S. Braunfels, K. Meinhard, B. Zieher, K. P. Koetter, W. H. Maleck, andG. A. Petroianu, “A randomized, controlled trial of the efficacy ofclosed chest compressions in ambulances,” Prehosp, Emerg. Care 1997July-September; 1(3):128-31) have shown that, in the absence offeedback, CPR is often administered ineffectively. The disclosures ofthese references are incorporated herein by reference

In any of the above mentioned embodiments of the invention, motion ofthe head relative to the electrodes, coils, or sensors can produce aspurious change in measured blood volume, and hence a spuriouscalculated blood flow. Various methods are optionally used to reducesuch motion artifacts. For example, the effect of any motion that is notcorrelated with the pulse cycle is optionally reduced by averaging overtime. Such averaging will not eliminate motion artifacts in thecalculated blood flow due to motion that is correlated with the pulse,such as motion associated with the administration of CPR. Motionartifacts are also optionally reduced by keeping the head immobilized,and keeping the electrodes, coils, and sensors rigidly in place againstthe head. Optionally, motion artifacts are compensated for by using anaccelerometer to detect motion of the head, and modeling the motionartifacts, or by only using data taken when the head is not moving toomuch. Additionally or alternatively, a pulse detected in the neck isused to distinguish motion artifacts from the real effects of blood flowin the brain, even if the pulse in the neck is not usable for measuringblood flow directly.

Potential applications of these techniques for measuring blood flow inthe brain may best be served by adapting the device to each application.For example:

1) For emergency medical situations such as arrhythmia, myocardialinfarction, cardiac arrest, or traumatic hemorrhagic shock, the deviceis optionally made portable, with a self-contained power supply, perhapsbattery operated, and/or has a monitor with only limited informationdisplayed.

2) For follow-up of traumatic brain injury patients, the deviceoptionally is portable enough and rugged enough for home use, using abattery or AC power from a wall outlet, and/or has a monitor that issimple enough to be used by the patient or a family member with littletraining, and optionally also displays additional information that couldbe used, for example, by a visiting nurse.

3) For monitoring blood flow to the brain prior to and during surgicalprocedures, especially carotid endarectomy, the device need not beportable or could be moved around on a cart, and optionally displaysdata that would be of interest to the surgeon or other medical personnelin the operating room, so that changes can be made in the surgicalprocedure in real time, in response to a decrease in blood flow, forexample.

4) For monitoring patients suffering from diseases such as stroke,syncope, and sickle cell anemia, where disturbances in cerebral bloodflow often occur, the device optionally measures local blood flow indifferent regions of the brain, and optionally comes in differentversions, one for hospital use, for example in an intensive care unit,and one for long term monitoring at home.

5) For use in a neonatal intensive care unit, the device need not beportable, but the electrodes or coils and sensors are optionally of asize, shape and/or attachment method adapted for use in newborn andpremature babies. The monitor is optionally integrated with othermonitors of vital signs, and configured to sound an alarm, for example,at a nurse's station, if a significant change in cerebral blood flow isdetected. Optionally, the monitor also records activities, times and/ortreatments which affect blood flow adversely.

6) For cardiopulmonary resuscitation (CPR), to verify that it is workingeffectively, the device optionally integrates the blood flow in thebrain after every few chest compressions, for example every time thelungs are expanded, and prominently displays the result on a large dialor array of lights, so the person administering CPR can immediately seewhether the chest compressions are too weak or too strong, or too slowor too fast, or whether the heart has started beating on its own. Aportable version of the device is optionally used by emergency medicaltechnicians in the field or in an ambulance. A less portable version, ona cart for example, is optionally used in a hospital emergency room.

For these applications, accurate measurements of blood bow to the brainare not necessarily needed, but it is important to detect large changesin blood flow, or the presence or absence of blood flow. The potentialfor low cost of the system, and the fact that it can be used by someonewith relatively little training, is important for these applications,especially for CPR. Other potential advantages of this technique overexisting methods of measuring blood flow in the brain, for example TCD,include the fact that it measures blood flow continuously in real time,the fact that it operates automatically without the need for an operatorwhose sole function is to run the equipment, the fact that it measuresglobal rather than local blood flow, and the small size and portabilityof the equipment in some embodiments of the invention.

As used herein, “two portions of a same electrode” includes the case oftwo separate electrodes that are electrically shorted together.

The invention has been described in the context of the best mode forcarrying it out. It should be understood that not all features shown inthe drawings or described in the associated text may be present in anactual device, in accordance with some embodiments of the invention.Furthermore, variations on the method and apparatus shown, which will bereadily apparent to and may be readily accomplished by persons skilledin the art, are included within the scope of the invention, which islimited only by the claims. Also, features of one embodiment may beprovided in conjunction with features of a different embodiment of theinvention. The words “comprise”, “include” and their conjugates as usedherein mean “include but are not necessarily limited to”.

1-44. (canceled)
 45. An apparatus for estimating blood flow to a brain,the apparatus comprising: a controller configured to: receive anelectrical signal from at least a first pair of electrodes adapted toengage a subject's head when electricity flows between at least a secondpair of electrodes adapted to engage with the subject's head; measurethe electrical signal; generate at least one impedance measurement ofvariation associated with a pulse cycle usable to estimate the rate ofblood flow to the brain from the measured electrical signal; generate anaverage impedance measurement; receive a signal indicative of a pulserate; and estimate the rate of blood flow to the brain based on the atleast one impedance measurement, the average impedance measurement, thesignal indicative of the pulse rate, and an estimate of a total brainblood volume.
 46. The apparatus according to claim 45, wherein a totalspread of the first pair of electrodes and the second pair of electrodeson a side of the head is at least 1 cm.
 47. The apparatus according toclaim 45, wherein a total spread of the first pair of electrodes and thesecond pair of electrodes on a side of the head is at least 2 cm. 48.The apparatus according to claim 45, wherein a total spread of the firstpair of electrodes and the second pair of electrodes on a side of thehead is at least 5 cm.
 49. The apparatus according to claim 45, furthercomprising at least one structure through which at least one of thefirst pair of electrodes is mechanically connected to at least one ofthe second pair of electrodes.
 50. The apparatus according to claim 49,wherein the at least one structure is rigid.
 51. The apparatus accordingto claim 45, wherein the at least one impedance measurement includes ameasurement of impedance amplitude.
 52. The apparatus according to claim45, wherein the at least one impedance measurement includes ameasurement of impedance phase and the estimate of the rate of bloodflow to the brain is further based on the measurement of impedancephase.
 53. The apparatus according to claim 45, wherein the electricityflow includes an alternating current signal component of between 40 kHzand 100 kHz.
 54. The apparatus according to claim 45, further comprisingan accelerometer configured to detect head movement, wherein the atleast one controller is further configured to reduce motion artifactsusing data from the accelerometer.
 55. The apparatus according to claim45, further comprising a monitor configured to display informationrelated to the estimated blood flow.
 56. The apparatus according toclaim 55, wherein the monitor is further configured to alert a user to asignificant change in estimated blood flow.
 57. The apparatus accordingto claim 45, wherein the at least one controller is further configuredto reduce motion artifacts based on the signal indicative of the pulserate.
 58. The apparatus according to claim 45, wherein the controller isfurther configured to estimate the rate of blood flow to the brain usinga calibration relationship between the at least one impedancemeasurement, the average impedance measurement, the estimate of totalbrain blood volume, and a change in blood volume over a pulse cycle. 59.A method of estimating blood flow in the brain of a subject, the methodcomprising: causing currents to flow inside the brain by engaging atleast two pairs of current-carrying electrodes with the subject's headand applying a voltage to each of the at least two pairs ofcurrent-carrying electrodes; measuring changes in the currents;generating an average current measurement; receiving a signal indicativeof a pulse rate of the subject; estimating changes in blood volume ofthe head, using the measurements of the currents, the average currentmeasurement, and an estimate of total brain blood volume; and estimatinga rate of blood flow in the brain based, at least in part, on thechanges in the blood volume of the head and the pulse rate.
 60. Themethod according to claim 59, wherein the voltage applied to each of theat least two pairs of current-carrying electrodes is different for eachpair of current-carrying electrodes.